S-Nitrosoglutathione ameliorates acute renal dysfunction in a rat model of lipopolysaccharide-induced sepsis

被引:21
作者
Samuvel, Devadoss J. [1 ]
Shunmugavel, Anandakumar [2 ]
Singh, Avtar K. [1 ]
Singh, Inderjit [2 ]
Khan, Mushfiquddin [2 ]
机构
[1] Med Univ South Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA
[2] Med Univ South Carolina, Dept Pediat, Charleston, SC 29425 USA
关键词
acute kidney injury; lipopolysaccharide; renoprotection; sepsis; S-Nitrosoglutathione; ACUTE KIDNEY INJURY; SPINAL-CORD-INJURY; NITRIC-OXIDE; NITROSYLATION; INHIBITION; GLUTATHIONE; KINASE; INFLAMMATION; MACROPHAGES; ACTIVATION;
D O I
10.1111/jphp.12608
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Objective Sepsis induces an inflammatory response that results in acute renal failure (ARF). The current study is to evaluate the role of S-Nitrosoglutathione (GSNO) in renoprotection from lipopolysaccharide (LPS)-induced sepsis. Methods Rats were divided to three groups. First group received LPS (5 mg/kg body weight), second group was treated with LPS + GSNO (50 mu g/kg body weight), and third group was administered with vehicle (saline). They were sacrificed on day 1 and 3 post-LPS injection. Serum levels of nitric oxide (NO), creatinine and blood urea nitrogen (BUN) were analysed. Tissue morphology, T lymphocyte infiltrations, and the expression of inflammatory (TNF-alpha, iNOS) and anti-inflammatory (IL-10) mediators as well as glutathione (GSH) levels were determined. Key finding Lipopolysaccharide significantly decreased body weight and increased cellular T lymphocyte infiltration, caspase-3 and iNOS and decreased PPAR-c in renal tissue. NO, creatinine and BUN were significantly elevated after LPS challenge, and they significantly decreased after GSNO treatment. TNF-alpha level was found significantly increased in LPS-treated serum and kidney. GSNO treatment of LPS-challenged rats decreased caspase-3, iNOS, TNF-alpha, T lymphocyte infiltration and remarkably increased levels of IL-10, PPAR-gamma and GSH. Conclusion GSNO can be used as a renoprotective agent for the treatment of sepsis-induced acute kidney injury.
引用
收藏
页码:1310 / 1319
页数:10
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